LAUSR

Background: Incidence rates of hepatocellular carcinoma (HCC) has been increasing for several decades in the U.S. Non-alcoholic liver disease (NAFLD) increasingly plays a role in the rising rate of HCC. Experimental data have shown that bile acids, which play key roles in the host-gut microbiota co-metabolism, contribute to the development of NAFLD and HCC. We propose to comprehensively examine the associations of bile acids with risk of HCC in two cohorts. Methods: Thirty-five bile acids were quantified using the state-of-the-art ultraperformance liquid chromatography triple-quadrupole mass spectrometry assays in serum samples collected, on average, five years prior to diagnosis of 197 HCC and the same number of individually matched controls from the Singapore Chinese Health Study and the Shanghai Cohort Study. Conditional logistic regression was used to assess the associations for major bile acids and their conjugates, and bile acid ratios with the risk of HCC. Results: Total primary bile acids were significantly elevated whereas the ratio of secondary bile acids over primary bile acids were significantly lower in HCC cases than controls in both cohorts (P9s ≤ 0.001). Doubling of tauro- vs. glyco-conjugates of all bile acids, primary bile acids, and specifically chenodeoycholic acid resulted in an increase in HCC risk of 44, 48, and 34% (P = 0.004, Conclusion: Primary bile acids, especially tauro-conjugated bile acids were strongly associated with increased risk of HCC risk whereas the secondary vs. primary bile acids ratios were associated with decreased risk of HCC. Citation Format: Claire Elizabeth Thomas, Hung Luu, Renwei Wang, Guoxiang Xie, Jennifer Adams-Haduch, Aizhen Jin, Woon-Puay Koh, Wei Jia, Jaideep Behari, Jian-Min Yuan. Conjugated primary bile acids as a biomarker for hepatocellular carcinoma risk in two prospective cohorts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 748.